Regulation of the Lactose Operon
Structure and Genes Lac ''genes are inducible genes that are expressed in the presence of lactose, the inducer, in the environment. The inducer can control the expression of the structural ''lac ''genes involved in the metabolism of lactose. Certain antibiotics can induce the expression of a gene that can lead to resistance of the antibiotic. Induction is common in metabolic pathways that result in the catabolism of a substance and the inducer is normally the substrate for the pathway. The lactose operon contains three structural genes that code for enzymes involved in lactose metabolism. 1) The ''lac Z gene codes for ß-galactosidase. ß-galactosidase is the enzyme that breaks down lactose into glucose and galactose. 2) The lac ''Y gene codes for lactose permease. This is involved in the uptake of lactose. 3) The ''lac ''A gene codes for a thiogalactosie transacetylase. These genes are transcribed from a common promoter into a polycistronic mRNA, which is translated to yield the three enzymes. The operon also contains a promoter, terminator, regulator, and operator. The ''lac ''operon the operon that is required to transport and metabolize lactose in ''Escherichia Coli ''(E. coli) and in some other intestinal bacteria. Lactose permease is located in the cytoplasmic membrane. It is what transports lactose into the cell. ß-galactosidase separates lactose into glucose and galactose. The lac operon has two parts to its control mechanism, which allows the operon to ensure that the cell will only use energy to produce enzymes that it encodes and only when needed. When there is no lactose present, the ''lac repressor stops the production of the enzymes that the operon codes for. Furthermore, the catabolite activator protein (CAP) is inactive when glucose is present, and EIIAGic shuts down lactose permease. This prevents the uptake of lactose. This two-step mechanism, allows for the sequential utilization of glucose and lactose. Regulation The availability of lactose is what controls the production of the lac ''genes, and the proteins are not coded for when lactose is not present. The ''lac ''genes are co-transcribed into one polycistronic mRNA molecule. RNA polymerase (RNAP) binds to the promoter, which is located immediately upstream of the genes, with the help of CAP. Once they are bound, RNAP begins to transcribe the three ''lac ''genes into mRNA. The regulatory response uses the lactose repressor, an intracellular regulatory protein, to stop the production of ß-galactosidase in the absence of lactose. The lacl gene codes it for, which is constitutive. When lactose is absent, the repressor binds to a short DNA sequence that is located downstream of the promoter and near the beginning of the operator, or ''lac Z. It interferes with the binding of RNAP to the promoter, which reduces the LacZ and LacY levels. When lactose is present, alllactose, a lactose metabolite that is a combination of glucose and galactose, binds to the repressor and alters its shape, preventing it from binding to the operator and allowing RNAP to transcribe the lac genes. When there is glucose absent in the system, CAP and cAMP concentrations are high. cAMP binds to CAP and CAP binds to the CAP binding site, which helps RNAP bind to the DNA, increase ß-galactosidase production, hydrolyze lactose, and release galactose and glucose. The PEP-dependent phosphotransferase system can transport glucose into the cell and block ''lac ''operon expression. The phosphate group from phosphoenolpyruvate is transferred through a phosphorylation cascade, where EIIBGic phosphorylates it and drains the phosphate group from the other PTS proteins. The unphosphrylated EIIAGic binds to the lac permease and preents it from bringing lactose into the cell. When both glucose and lactose are present, glucose blocks the transport of the inducer and stops the production of ''lac ''genes.